1. Field of the Invention
This invention relates to a novel method for increasing fertility in males with impairment of testosterone synthesis by injecting slow-release microcapsules or microspheres containing testosterone directly into infertile testes to stimulate Leydig cells. 2. Prior Art
Approximately 5 percent of American couples are infertile due to male infertility alone (approximately 2.5 million men), and 75 percent of these males have pathologies associated with low testosterone output by the testes (approximately 1.9 million men). Direct testicular injection of slow-release testosterone encapsulations could be efficacious in increasing the fertility of many of these men.
No thought has apparently been given to the method of using testosterone-laden microspheres for fertility enhancement rather than fertility reduction. Testosterone is required for spermatogenesis. Normally, the Leydig cells of the testes secrete testosterone directly into the testicle interstitial fluid and maintain the locally high testosterone concentration required for the maintenance of robust spermatogenesis. In some males, this fails to occur. Leydig cells either fail to produce testosterone at all, or fail to secrete it in sufficient amounts to maintain normal spermatogenesis.
Microcapsulation of bioactive compounds (primarily steroid hormones) has been performed for almost ten years. The microcapsulation process itself is covered by U.S. Pat. No. 4,489,330.
Beck et al first reported the use of biodegradable microspheres for the encapsulation of a steroid hormone and the intramuscular injection of those microspheres as a long-acting method for the slow-release of norethisterone into the bloodstream (Beck et al., "New Long-Lasting Injectable Microcapsule Contraceptive System", J. OBSTET. GYN., 135:419-426 (1979)). The concept was to provide a method of long-term steroid delivery for women for purposes of contraception. This work has been followed up by studies which examine the efficiency of this contraceptive delivered to human females (Beck et al., "Clinical Evaluation of Injectable Biodegradable Contraceptive System", AM. J. OBSTET. GYNEC., 140:799-806 (1981); Beck et al., "Clinical Evaluation of and Improved Injectable Microcapsule Contraceptive System", AM. J. OBSTET. GYNEC, 147:815-821 (1983); Rivera et al., "Norethisterone Microspheres Six-Month System: Clinical Results", Long-Acting Contraceptive Delivery Systems, Harper and Row (1984)). Since at least 1980 there has been work on the encapsulation of other hormones in biodegradable microspheres, and in 1986 a method was disclosed for the manufacture of testosterone--containing biodegradable microspheres (Lewis et al., "Overview of Controlled Release Systems of Male Contraception" and Asch et al., "Preliminary Results on the of Testosterone Microcapsules", Male Contraception: Advances and Future Prospects, Harper and Row (1986)). These were developed with the thought of using such microspheres in applications towards male contraception or virilizing males with hypopituitary or hypogonadal function.